The history of clozapine

Clozapine: More Side Effects but Still the Best Antipsychotic

“…We were able to confirm Haase's findings and also showed that clozapine did not produce cramping of handwriting. 1,2 In our small-sample study, 2 clozapine was shown to be active and to produce sedation and salivation, but no EPS. Tardive dyskinesia that was present in 2 patients improved.…”

“…Hippius 1 documented this history well, but, in essence, at a time when everyone believed that antipsychotic activity and extrapyramidal symptoms (EPS) were inseparable. Wander AG laboratories, Basel, Switzerland, developed clozapine, which does not produce EPS.…”

Antipsychotic dosing: found in translation

“…In fact, clozapine was initially investigated as an antidepressant and was almost shelved after its release owing to unexpected deaths that were later linked to agranulocytosis. 6 The point to be made, though, is that while we allot considerable weight and resources to the search for these major paradigm shifts, they are few and far between. In the meantime, there is the opportunity to make important and immediate advances in clinical care by ensuring that we are using what we have at hand as best as possible.…”

Drug treatment developments in schizophrenia and bipolar mania: latest evidence and clinical usefulness

“…Unveiled a decade after the launch of chlorpromazine, all antipsychotics antagonize dopaminergic transmission at the dopamine D2 receptor subtype, which has proven to be essential to the antihallucinatory and antidelusional effects of the drugs [Howes and Kapur, 2009]. The potent D2-blocking property of the early antipsychotics is also associated with hyperprolactinaemia and the extrapyramidal syndrome (EPS), including Parkinsonism, akathisia and tardive dyskinesias, which was considered by many an obligatory side effect until the demonstration of clozapine's 'atypical' combination of stronger antipsychotic action without causing significant EPS or prolactin elevation [Cookson et al 2012;Hippius, 1989]. The class of drugs following clozapine aimed at mimicking the 'atypical' properties, and was accordingly termed atypicals or second-generation antipsychotics (SGAs) as opposed to the older typical or first-generation drugs (FGAs).…”